Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting.

Introduction: The prognostic significance of steroid receptors in bladder cancer remains controversial. This study was designed to determine the expression status of androgen receptor (AR), estrogen receptors (ERα and Erß), and its potential role in predicting survival in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Sixty patients of NMIBC were screened and 57 (41 males and 16 females) were included in our study. The tissue microarray slides were evaluated by pathologists blinded to the clinical information. Association of distribution of steroid receptors with stage, grade, progression, and recurrence was seen. Results: The mean age of the population was 60.9 ± 9.3 years. Pathologically, majority of the patients were Ta (Ta: T1 stage 61.4% vs. 38.6%). Nine (15.8%) of the tumors stained positive for AR while one (1.8%) tumor stained positive for ERα and 36 (63.2%) tumors stained for ERß. A higher proportion of male NMIBC stained positive for AR (19.5% vs. 6.2%, P = 0.420) while ERß positivity was higher in females (58.5% vs. and 75%,P = 0.247). AR-negative tumors showed higher recurrence (20/48%-42%) as compared to AR-positive tumors (2/9%-22%). ERß-positive tumors showed higher recurrence (15/36%-42% vs. 7/21%-33%, P = 0.179). Progression-free survival (PFS) was found to be significantly lower for ERß-negative group (log-rank test P = 0.035). Conclusion: AR and ERß positivity is found in NMIBC patients while ERα shows minimal staining in NMIBC patients. Although it did not reach a statistical significance, a higher proportion of AR-negative and ERß-positive tumors recurred as compared to AR-positive and ERß-negative patients. PFS was significantly lower in ERß-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.

Safety and Diagnostic Yield of 68Ga Prostate-specific Membrane Antigen PET/CT-guided Robotic-assisted Transgluteal Prostatic Biopsy.

Background Transrectal US-guided biopsy with or without MRI fusion is performed for diagnosing prostate cancer (PCa) but has limitations. Gallium 68 (68Ga) prostate-specific membrane antigen (PSMA) PET/CT-guided targeted biopsy has the potential to improve diagnostic yield of PCa. Purpose To evaluate the safety and diagnostic yield of 68Ga PSMA PET/CT-guided, robotic-arm assisted transgluteal prostatic biopsy. Materials and Methods In this single-center nonrandomized prospective trial, participants with a clinical suspicion of PCa (serum prostate-specific antigen level > 4 ng/mL) were recruited from January 2019 to September 2020. After whole-body 68Ga PSMA PET/CT, participants with PSMA-avid intraprostatic lesions underwent PET-guided transgluteal biopsy by using an automated robotic arm. To assess safety and diagnostic yield, procedure-related complications and histopathologic results were documented. Pain during the procedure was scored by a visual analog scale. Descriptive statistics were applied; qualitative variables were reported in percentages. Results Seventy-eight participants (mean age, 66 years ± 7 [standard deviation]; 36 participants [46%] with prior negative results at transrectal US-guided biopsy) were enrolled. Fifty-six (72%) participants had PSMA-avid lesions (prior negative results at transrectal US-guided biopsy in 22 of 56 [39%]) and underwent targeted biopsy. PCa was confirmed in 54 of 56 (96%) participants, and clinically significant PCa (Gleason score ≥ 7) was confirmed in 24 of 54 (44%). Two participants had nonrepresentative samples that required rebiopsy. All participants experienced pain during the procedure, mild (median visual analog scale score, 1; interquartile range, 1-2) in 36 of 56 (64%) and moderate (median visual analog scale score, 5; interquartile range, 5-6) in 20 of 56 (36%). Postprocedure complications were noted in five of 56 (9%) participants and were minor (hematuria, four participants; hematospermia, one participant; and gluteal pain, two participants). No participant developed a postprocedural infection. Conclusion Transgluteal prostate-specific membrane antigen (PSMA) PET/CT-guided, robotic-targeted prostatic biopsy is safe with a high diagnostic yield of prostate cancer for PSMA-avid lesions. Clinical trial registration no. NCT05022576 © RSNA, 2022.

A higher tumor volume and undernutrition at diagnosis adversely affect the survival of children with Wilms tumor: A study of 200 patients.

BACKGROUND: Distinct prognostic factors for Wilms tumor (WT) in low- and middle-income countries need identification. METHODS: Retrospective study of patients with WT managed by the International Society of Pediatric Oncology (SIOP) approach for over 11 years (2005-2016) at a single center in Chandigarh, India. RESULTS: The study included 200 patients (median age: 33.5 months). The tumor stage (SIOP) distribution included stage I (30%), II (36%), III (14%), IV (17%), and V (3%). The histology-risk groups were low (8%), intermediate (84%), and high risk (9%). At diagnosis, 68 out of 190 (36%) patients were underweight. The median tumor volume at diagnosis was 481 ml (interquartile ratio [IQR]: 306.9, 686.8, n = 146). Following neoadjuvant chemotherapy, it reduced to 110 ml (IQR: 151.2, 222, n = 77). Treatment was abandoned in 20.5% of the patients. Treatment-related mortality occurred in 13 of 179 (7.2%) patients. Relapse occurred in 26 of 158 (16.5%) patients. The 3-year overall survival (OS) and event-free survival (EFS) of patients who completed therapy were 78.3 and 72%, respectively. The stage (p = .013) and histology (p = .023) influenced OS. A lower OS in stage II (75.4%) versus stage III disease (83.7%) suggested understaging. Patients with a higher tumor volume at diagnosis (p = .005; odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.99-1.00) or a lower weight-for-age z-score (p = .002; OR: 1.68; 95% CI: 1.21-2.33) had an increased risk of death or relapse. CONCLUSIONS: The 3-year OS and EFS of children who completed therapy were 78.3 and 72%, respectively. A higher tumor volume and lower weight-for-age z-score at diagnosis were identified as distinct adverse prognostic factors. A likely suboptimal lymph node assessment (intraoperative and histopathology) contributed to the understaging of stage III to II disease and reduced survival.

Facility-based stillbirth surveillance review and response: an initiative towards reducing stillbirths in a tertiary care hospital of India.

OBJECTIVES: India has the highest number of stillbirths in the world in 2019, with an estimated stillbirth rate of 13.9 per 1,000 births. Towards better identification and documentation, a stillbirth surveillance pilot was initiated with the World Health Organization Southeast Asia collaboration in Northern India in 2014. This study aimed to assess whether stillbirth surveillance is feasible and whether this approach provides sufficient information to develop strategies for prevention. METHODS: This study followed the framework provided in "WHO Making Every Baby Count" in which mortality audit is conducted in six steps; (1) identifying cases; (2) collecting information; (3) analysis; (4) recommending solutions; (5) implementing solutions; and (6) evaluation. RESULTS: A total of 5,284 births were examined between December 2018 and November 2019; 266 stillbirths were identified, giving a stillbirth rate of 50.6 per 1,000 births in a tertiary care referral hospital of northern India. Out of 266 stillbirths, 223 cases were reviewed and recommendations were formulated to strengthen obstetric triage, implementing fetal growth charts, strengthen the existing referral system and improve the communication skills of health care providers for better compliance with clinical practice guidelines. CONCLUSIONS: Conducting stillbirth surveillance review and the response of cases in low-middle income countries setting is feasible. As countries progress towards ending preventable mortality, this has the potential to serve as a key process in improving evidence-based and context-specific planning and preventive strategies towards improving the quality of care.

Outcome of pediatric germ cell tumor with comparison of carboplatin and cisplatin based regimens: A 10-year analysis.

Carboplatin is being advocated more frequently for treatment of childhood germ cell tumors (GCT), due to less long-term toxicity, and demonstrable equivalence in outcome as compared to cisplatin. This analysis presents the survival of GCT in a low middle-income country and compares two different chemotherapeutic regimens. A retrospective analysis of patient case records was carried out over 10-years (January 2007-December 2016). Chemotherapy regimen used was bleomycin, etoposide, and cisplatin (PEb) for initial 6-½ years and carboplatin, etoposide, and bleomycin (CEb) subsequently. Ninety patients with GCT were treated over 10-years. Malignant GCT was diagnosed in 69 (77%) patients, with 21(23%) having teratoma. The chemotherapy protocol was PEb in 38 (42%), CEb in 28 (31%) patients, while 24 patients were treated with surgery only. Stage 4 tumor was observed in 19 (21%) patients. Relapse or disease progression was seen in 11(12%). Overall and event-free survival at 5-years for the entire cohort was 77% and 73%, being similar with PEb (OS:77%; EFS:72.5%) vs. CEb (OS:69%; EFS: 69%). Significantly better overall survival was noted for patients with gonadal GCT) and non-stage 4 disease, while event-free survival was significantly better in patients with non-stage 4 disease. The chemotherapeutic regimen (PEb vs. CEb), very high AFP (value ≥10,000 IU/L), and risk stratification (low, intermediate, or high-risk disease) did not affect survival significantly. Carboplatin-based strategy was equivalent in our cohort to cisplatin-based strategy, and could be used safely in the LMIC set-up. The overall survival is suboptimal, with delayed presentation, abandonment, and relapse being barriers to survival.

Retrospective single-center experience with OEPA/COPDAC and PET-CT based strategy for pediatric Hodgkin lymphoma in a LMIC setting.

ABVD regimen for Hodgkin lymphoma (HL) is frequently used in children and young adults in low-middle income countries (LMIC). The feasibility and safety data for 'non-ABVD' protocols from LMIC is limited. The retrospective study was conducted in a single center in India. The Euronet PHL-C1 based protocol was administered during 2010-19. A PET-CT was performed at diagnosis and following two OEPA cycles. Radiotherapy was administered for inadequate PET response. During the 10-year period, 143 patients with HL were treated. The mean age was 7.8 ± 2.5 years. Bulky disease was observed in 82 (59%). Treatment abandonment was recorded in 13 (9.1%). The median follow-up duration was 46.4 months. An inadequate PET response was observed in 41/119 (34.4%), of which 56.1% received radiotherapy. Twelve (29.3%) patients who were supposed to receive radiotherapy received 2-cycles of COPDAC instead. Sixty-nine episodes of febrile neutropenia were observed in 54 patients. Treatment-related mortality (TRM) was observed in 7 (5.3%). The majority of episodes of febrile neutropenia (61%) and TRM (86%) occurred in the first cycle of OEPA. The 4-year event-free survival (EFS) and overall survival (OS) were 86.2 ± 3.4% and 93.5 ± 2.2%, respectively. Nine (6.3%) patients relapsed. Bulky disease lacked association with inadequate PET response (p = .800) or relapse (p = 1.000). OEPA/COPDAC regimen and response assessment by PET-CT permitted therapy reduction, including radiotherapy. Febrile neutropenia and resultant TRM (5.3%) are concerning and occurred frequently in the first cycle of OEPA. The support system for managing febrile neutropenia should be optimized for administering OEPA in LMIC.

Diagnostic accuracy and cytomorphological spectrum of Wilms tumour in fine needle aspiration biopsy cytology samples supplemented with cell blocks.

OBJECTIVE: Paediatric malignant renal neoplasms are subjected to neoadjuvant chemotherapy as per Societe Internationale d'Oncologie Pediatrique; International Society of Pediatric Oncology (SIOP) protocol. An accurate tissue diagnosis is required prior to institution of chemotherapy, and hence the aim of this study was to evaluate the diagnostic accuracy of fine needle aspiration biopsy cytology (FNABC) along with cell block histology. MATERIALS AND METHODS: A retrospective audit of all paediatric renal neoplasms diagnosed by FNABC between 2015 and 2019 was performed. Histopathology correlation was done wherever available. WT cases were subjected to detailed cytomorphological evaluation. RESULTS: A total of 121 cases of paediatric renal neoplasms including 109 WT, four clear cell sarcoma, one malignant rhabdoid tumour and three mesoblastic nephroma were evaluated. The age range was 4 weeks to 8 years. FNABC samples were adequate for diagnosis in 120 of 121 cases (99.18%) and a definitive cytological diagnosis was achieved in 117 cases (96.7%). The specificity and sensitivity for a cytopathological diagnosis of WT were 98.7% and 97.4%, respectively. On detailed cytomorphological analysis of 68 histopathology-proven WT, 40 (58.8%) cases were triphasic, 23 (35.3%) were biphasic and four were composed of blastema only. The corresponding cell blocks provided additional information over the conventional smears in 23 (33.8%) cases, with epithelial or mesenchymal elements recognised and evidence of rhabdomyoblastic differentiation. CONCLUSION: FNABC along with cell block histology is highly accurate for diagnosis of WT and other malignant paediatric renal neoplasms and is recommended as the technique of choice in centres with cytopathology expertise for establishing a cellular diagnosis prior to commencement of neoadjuvant chemotherapy.

Prevalence & spectrum of congenital anomalies at a tertiary care centre in north India over 20 years (1998-2017).

Background & objectives: Congenital anomalies lead to significant morbidity and mortality. Systematically published data on the prevalence and spectrum of congenital anomalies from India are scarce. This study was aimed to ascertain the prevalence, spectrum, trend, and outcome of congenital anomalies at a tertiary care centre in north India over two decades. Methods: Electronic records of all live births from January 1998 to December 2017 were retrieved, and the neonates with congenital anomaly were included in this retrospective analysis. International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) was used for uniformity and international comparison. The further sub-categorization was done as per the WHO birth defects surveillance manual. The prevalence of individual as well as overall congenital anomalies was calculated. Run charts were used to analyze the trends. Results: In the two decades studied (1998-2017), there were 86850 live births, of which 1578 [1.82%, 95% confidence interval (CI): 1.73-1.91%] neonates had a major congenital anomaly. The overall prevalence of anomalies was 182 (95% CI: 173-191) per 10,000 live births. Malformation of the circulatory system was the most common (28.0%) followed by musculoskeletal (18.6%) and urinary system (14.3%). Congenital anomaly-related death rate was 6.78 per 1000 live births. No significant trend was observed in the annual prevalence, individual malformations or contribution of congenital anomalies to overall mortality over the two decades. Interpretation & conclusions: Our results showed a high prevalence of congenital anomalies which could be responsible for significant mortality, warranting the need for a national surveillance programme and birth defect services. It is important to have a national database to know the overall burden and spectrum of congenital anomalies in the country.

Syndrome of progressive deforming non-inflammatory arthritis of childhood: two patients of camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a rare familial arthropathy of childhood, commonly misdiagnosed as juvenile idiopathic arthritis. It is characterized by non-inflammatory arthropathy, coxa vara deformity, and sterile pericarditis. We describe two children with CACP syndrome who were referred to the rheumatology clinic for the suspicion of inflammatory arthritis. A literature search was carried out using PubMed/ Medline and Embase databases. English language reports of mutation-proven cases of CACP syndrome reported until 31 March 2020 were retrieved and analysed. Both the children had a delay in diagnosis (age at diagnosis- 12 and 13 years, respectively) and had received immunomodulatory therapy for suspected inflammatory arthritis. Presence of symmetrical arthropathy of large joints, camptodactyly, and normal inflammatory parameters are clues that indicated CACP syndrome. One child with a novel variant in PRG4 also had associated mitral valve prolapse and regurgitation. Both had severe constrictive pericarditis requiring pericardiectomy. On literature review, a total of 98 mutation-proven cases of CACP syndrome have been reported till date. Arthropathy in CACP syndrome mainly involves knees, wrists, ankles, and hips. Pericarditis is usually mild, however, can present rarely with severe symptoms requiring surgical intervention. CACP syndrome can closely mimic inflammatory arthritis and early clinical recognition is important to avoid misdiagnosis. Molecular confirmation is essential for early diagnosis and future genetic counselling for affected families.

Primary primitive neuroectodermal tumour of the kidney in adults: Experience of managing 12 cases with systematic review and pooled analysis of literature.

INTRODUCTION: Primitive neuroectodermal tumor (PNET) of the kidney is unusual in adults. These tumours are diagnosed mainly on histopathology and that too sometimes has limitations. With this study, we aimed to review our clinical and histopathological data of patients with renal PNET and reviewing the world literature. METHODS: In this retrospective study, we reviewed our database from January 2006 to July 2018 to include all the cases of primary PNET of the kidney. We also performed systematic literature search to identify all the relevant series on renal PNET. RESULTS: A total of 12 patients including 5 men and 7 women were managed during the above mentioned period. Out of these 7 patients, 2 patients had metastasis at diagnosis, one had locally advanced disease, 6 underwent radical nephrectomy, 5 patients received adjuvant chemotherapy (two currently receiving) and only 1 patient received adjuvant radiotherapy (RT). On Immunohistochemistry (IHC), CD99 and FLI1 were positive in all the patients. Median survival was 10 months. In our review 10 studies were included, 38.6% of the patients had metastatic disease and 10.7% had locally advanced disease at diagnosis. Overall mean survival was 33.75 months. CD99 and FLI1 were positive in 94.3% and 78.5%, respectively. CONCLUSION: PNET remains a pathological diagnosis and IHC has important place in diagnosis of PNET. Locally advanced and metastatic disease is common at diagnosis leading to overall poor survival.

Cytological diagnosis of osteosarcoma with emphasis on diagnostic pitfalls.

INTRODUCTION: Fine needle aspiration is a well-established technique for evaluating primary and secondary bony lesions. With use in selected cases, it achieves a diagnostic yield comparable to biopsies. METHODS: Cases of osteosarcoma (OS) with available histological follow-up were retrieved over a 10-year period. Detailed morphological evaluation was done, with special emphasis on pitfalls in the diagnosis of OS on cytology and the various variants of OS. RESULTS: Of the 41 cases with available follow-up histology, 56% were correctly diagnosed as OS on cytology. The most common false-negative cytological diagnosis of OS, in 17% cases, was giant cell tumour. The possible explanations for this included low cellularity, minimal atypia, absence of typical osteoid, misinterpretation of metachromatic osteoid material as fibro-collagenous material and non-availability of radiology at time of aspiration. CONCLUSION: A triple-phase evaluation including clinical evaluation, appropriate radiological correlation and cytology/histopathology, is important to clinch an accurate diagnosis.

Survival in patients with high-risk neuroblastoma treated without autologous stem cell transplant or dinutuximab beta.

The majority of patients with high-risk neuroblastoma (HR-NB) in low- and middle-income countries (LMIC) do not have access to autologous stem cell transplant (ASCT) and dinutuximab. Consolidation with nonmyeloablative chemotherapy is not well-defined, and the outcomes are variable. We report a single-center outcome of patients with HR-NB, treated with nonmyeloablative consolidation. A tabulated compilation of similar reports is included. A retrospective chart review of patients with HR-NB was performed from January 2009 till June 2016. Patients were treated on the backbone of HR-NBL1/SIOPEN protocol. Treatment included induction with rapid-COJEC, surgery, followed by consolidation. Consolidation involved 4 cycles of topotecan, vincristine, and doxorubicin (TVD) instead of ASCT. Infusion of vincristine and doxorubicin were modified for ease and to enable administration in the clinic. Subsequent treatment included radiotherapy to the primary tumor and differentiation therapy with isotretinoin. Over 7½ years, 28 patients with HR-NB were treated. Two (7%) patients had therapy-related mortality. A relapse or disease progression occurred in 11 (39%) patients at a median duration of 17 months (IQR: 5, 18). Treatment abandonment was observed in 4 (14%) patients. The median follow-up of disease-free patients was 49 months (IQR: 45, 79). Patients with relapse were not treated further. A 4-year EFS of 29.3% was observed when 4-cycles of TVD were administered instead of ASCT in patients with HR-NB. The study and the review will aid decision-making for care of patients in LMIC while considering the options of treatment for HR-NB if access to ACST and dinutuximab is lacking.

Classifying stillbirths in a tertiary care hospital of India: International Classification of Disease-perinatal Mortality (ICD-PM) versus cause of death-associated condition (CODAC) system.

A number of classification system are available to classify stillbirths, but there remains a lack of a uniform global system of classification. This study evaluated the feasibility of the ICD-PM classification system and COD-AC to classify the stillbirths and to discuss the interpretation of "the newer" classification system (ICD-PM) over the COD-AC system. Over a period of one year, out of 5776 total births 314 were stillborns with a stillbirth rate of 54 per 1000 total births. As per ICD PM Classification System, 69.1% of stillbirths were ante partum and rest intrapartum. The associated maternal conditions at the time of foetal death were also classified into five groups and maximum mothers (44.3%) were grouped under M4-medical/surgical disorders. According to COD-AC system of classification 90% of cases were assigned the cause of death, rest 10% remained unexplained. The ICD-PM and CODAC classification both seem to be feasible but ICD-PM clearly defines the time of foetal death and correlates feto-maternal dyad together.IMPACT STATEMENTWhat is already known on this subject? Classifying stillbirths is crucial to recognise the actual cause of foetal death and to gather the relevant information for planning the preventive strategies especially in low middle-income countries (LMICs) which contribute to 98% of total global burden of 2.6 million stillbirths annually. In literature CODAC system was found most suitable for low middle-income countries. In 2016, WHO proposed a newer system, i.e., ICD-PM: WHO application of ICD-10 to deaths during the perinatal period.What do the results of this study add? With ICD-PM classification stillbirths were categorised more clearly in different groups and feto-maternal condition were linked together along with both intrapartum and ante partum stillbirth which can help to set the priorities and future planning for prevention. The proportion of unexplained stillbirth has also reduced significantly compared to CODAC system.What are the implications of these findings for clinical practice and/or further research? CD-PM system of classification seems feasible and would facilitate the uniform and consistent stillbirth data even from LMICs for global comparison although more number of studies are needed for conclusion. The system has been changed to ICD-PM in our institute.

Trifecta and pentafecta outcomes following robot-assisted partial nephrectomy for hilar versus nonhilar tumors: A propensity-matched analysis.

INTRODUCTION: Hilar tumors are a unique subset of complex renal masses posing a potential surgical challenge during partial nephrectomy. The outcomes of hilar masses have not been compared to non-hilar renal masses of similar RENAL nephrometry score (RNS). In this study, we analyzed the outcomes of hilar versus nonhilar masses after a propensity score matching. METHODS: Prospectively maintained database of patients who underwent robot assisted PN between November 2014 and December 2018 was abstracted for hilar and nonhilar tumors. We performed propensity matching for baseline variables such as age, sex, body mass index, comorbidities, preoperative glomerular filtration rate, and RNS for each patient on the basis of propensity scores. RESULTS: We included 48 patients with hilar tumors and 153 with nonhilar tumors. On propensity matching, 41 patients were included in each group. The mean operative time (162.4 ± 48.9 min vs. 144.1 ± 38.8 min, P = 0.48), warm ischemia time (29.0 ± 8.8 min vs. 24.4 ± 8.2 min, P = 0.12), and the estimated blood loss (201.8 ± 184.7 ml vs. 150.6 ± 160.5 ml, P = 0.37) were not significantly different between the hilar and the nonhilar groups. Trifecta was achieved in only 14/41 (34.1%) of the patients in the hilar group as compared to 24/41 (58.5%) in the nonhilar group (P = 0.027). Logistic regression analysis identified that hilar location of the tumors was not an independent predictor of overall complications (OR 6.37, confidence interval [CI] 0.5-69.4, P = 0.4), trifecta (OR 0.38, CI 0.14-1.0, P = 0.051), and pentafecta outcomes (OR 0.4, CI 0.1-1.51, P = 0.17). CONCLUSIONS: Hilar location was associated with poorer trifecta outcomes compared to the nonhilar tumors. However, hilar location per se was not an independent predictor of overall complications and trifecta and pentafecta outcomes.

BRAF V600E mutation in childhood Langerhans cell histiocytosis correlates with multisystem disease and poor survival.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia of children with systemic involvement and poor outcome. The altered RAS-RAF-MEK-ERK cell signalling pathway due to somatic mutation of BRAF V600E is the most common genetic abnormality associated with the disease. In the current study, we highlight the frequency of BRAF V600E in our cohort of LCH cases (n = 31) and its relation with clinical outcome. On Real-Time PCR and Sanger sequencing, BRAF V600E was detected in 6/31 (19%) patients. All cases positive for BRAF V600E mutation had multisystem involvement/disseminated disease compared to BRAF mutation negative cases (100% v/s 41%, p = 0.0348). Univariate analysis also revealed significant correlation of mutation positivity with risk category (p = 0.09). The event free survival and overall survival at 36 months for BRAF mutation positive group compared to mutation negative group was 17% v/s 72% (Log rank test p = 0.0110) and 32.5% v/s 82% (p = 0.0330), respectively. In our study, BRAF V600E positivity was low (19%) however, all positive cases had multisystem involvement and a poor three year survival confirming BRAF V600E to be a poor prognostic marker.

Autologous stem cell transplant for high-risk neuroblastoma: Achieving cure with low-cost adaptations.

BACKGROUND: The majority of patients in low- and middle-income countries (LMIC) are unable to receive optimal therapy, including autologous stem cell transplant (ASCT) for high-risk neuroblastoma. Management is intensive and multidisciplinary; survival is often poor. We report a single-center outcome of high-risk neuroblastoma, with adaptations optimized for LMIC. PROCEDURE: The study was retrospective. Patients were treated on the backbone of the high-risk neuroblastoma study-1 of SIOP-Europe (HR-NBL1/SIOPEN) protocol with ASCT. Adaptations incorporated to decrease cost, requirement for inpatient admission, infections, and faster engraftment included (a) optional outpatient administration for rapid-COJEC, (b) two sessions of stem-cell apheresis, (c) storing stem cells at 2-6°C without cryopreservation for up to 7 days, (d) no central lines, (e) no antibacterial/antifungal/antiviral prophylaxis, (f) omitting formal assessment of cardiac/renal/pulmonary functions before ASCT, and (g) administration of pegylated granulocyte colony-stimulating factor on Day +4. RESULTS: Over 5 years 9 months, 35 patients with high-risk neuroblastoma were treated. Rapid-COJEC was administered over a median duration of 80 days (interquartile range: 77, 83). Conditioning regimen included melphalan (n = 7), oral busulfan-melphalan (Bu/Mel; n = 6), or intravenous Bu/Mel (n = 22). The median viability of stem cells stored for 6 days (n = 28) was 93% (range: 88-99). Two (5.7%) patients had ASCT-related mortality. The 3-year overall and event-free survival was 41% and 39%, respectively. A relapse occurred in 20 (57%) patients. Treatment abandonment was observed in one (3%) patient. CONCLUSIONS: Administration of therapy in a disciplined time frame along with low-cost adaptations enables to manage high-risk neuroblastoma with low abandonment and an encouraging survival in LMIC. Stem cells can be stored safely without cryopreservation for up to 7 days.

In vitro evidence of NLRP3 inflammasome regulation by histone demethylase LSD2 in renal cancer: a pilot study.

NLRP3 pathway plays a vital role in the pathogenesis of different human cancers but still the regulation of NLRP3 pathway largely unknown. Therefore, we examined the levels of NLRP3 and its downstream components (caspase-1 and IL-1ß) and its relationship with histone modifiers in renal cancer pathogenesis. Total 30 cases of clear cell renal cell carcinoma (ccRCC), were studied for NLRP3, caspase-1 and IL-1ß expression using real-time PCR, which showed the augmented levels of all the three components of NLRP3 inflammasome pathway in ccRCC. Next, role of the FAD dependent monoamine oxidases (LSD2) and jumonji C (JmjC)-domain-containing, iron-dependent dioxygenases (KDM5A) histone demethylases were evaluated in regulation of NLRP3 inflammasome pathway in-vitro using RCC cell line. It was observed that silencing of KDM5A didn't alter the levels of neither of the NLRP3 component but inhibition of LSD2 showed significant effect on NLRP3 expression while no change in caspase-1 and IL-1ß levels. This study suggests that rather LSD2 not KDM5A lysine demethylase family might be involved in the regulation of NLRP3 inflammasome in cancer cells which could be useful for deciphering the future therapeutic targets for the disease.

Copy Number Variations in Wilms Tumor: A Pilot Study From India.

BACKGROUND: The prognostic role of copy number variation is upcoming in Wilms tumor, and its identification will help in tailored therapy for improved cure. STUDY DESIGN: This was a retrospective, nested case-control, pilot study. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded blocks of nephrectomy specimens were retrieved for the study and control groups (children with relapse and survivors for ≥2 y). Multiplex ligand probe amplification (MRC-Holland probe-mix P 380 A1) was performed, with 3 reference samples of normal kidney DNA run for every 7 cases. RESULTS: At least 1 variation was detected in 41 (97.8%) specimens. Loss of heterozygosity 1p was not observed. Loss of 16q, 1q gain, and MYCN gain were observed in 5 (11.9%), 29 (69%), and 39 (92.9%) specimens, respectively. The occurrence of copy number variations was similar in both groups: 1q gain: 15 versus 14 (P=1.0), 16q loss: 4 versus 1 (P=0.34), MYCN gain: 19 versus 20 (P=1.0). The gain of 1q, 16p loss, and MYCN gain did not differ across stage or age. CONCLUSIONS: The gain of 1q, MYCN gain, and 16p loss were identified. A higher occurrence of 1q gain and MYCN gain and a lack of difference in the distribution of variations among survivors and those with a relapse suggest a different molecular profile of Wilms tumor in Indian children.

Facial Phaeohyphomycosis in an Immunocompetent Individual: A Rare Presentation of a Rare Fungus.

Phaeohyphomycosis is a rare mycotic infection caused by heterogenous groups of dematiaceous fungi involving the skin and subcutaneous tissue. Here, we report a case of cutaneous phaeohyphomycosis presenting as cauliflower-like verrucous lesion over the face in an immunocompetent individual. Histopathology showed suppurative granulomatous inflammation replete with pigmented broad fungal hyphae which is stained with periodic acid-Schiff stain, Grocott's methanamine silver stain, Schmorl's stain, and Masson-Fontana stain. Culture showed black-colored colonies identified as Exophiala spinifera.

Fine needle aspiration cytology of paediatric soft tissue tumours highlighting challenges in diagnosis of benign lesions and unusual malignant tumours.

INTRODUCTION: The type of soft tissue lesions seen in children differs from that seen in adults. The role of fine needle aspiration (FNA) cytology in their diagnosis is not well documented. AIM: To study the cytopathological spectrum of paediatric soft tissue tumours to highlight uncommon benign and malignant lesions and the challenges in their diagnosis. METHODS: A 3-year retrospective audit of all paediatric soft tissue FNA cytology cases from 2015 to 2017 was performed. Smears were reviewed along with cell block immunocytochemistry and follow-up histopathology of resected specimens wherever available. RESULTS: A total of 127 cases were reviewed, which included 72 benign and 55 malignant soft tissue tumours. Uncommon lesions described herein are myxoid fibrohistiocytic tumour, myxoma, lipoblastoma, Bednar tumour, malignant extra-renal rhabdoid tumour and desmoplastic small round cell tumour. Histopathology confirmation was available in 25 cases, out of which 16 cases were completely concordant. In eight cases, all benign diagnoses, histopathology provided more accurate subtyping than FNA. These included cases of lipoblastoma, myxoma and spindle cell haemangioma. CONCLUSION: FNA cytology of paediatric soft tissue tumours is accurate in classifying lesions as benign or malignant which helps in treatment planning. Immunocytochemistry performed on cell blocks is useful for subtyping malignant lesions.